Approach to bilateral lower limb oedema

Opening Vignette.

Mrs Tan, a 65-year-old Chinese lady, presents for routine follow-up of her chronic conditions. She has a past medical history of type 2 diabetes mellitus and hypertension. She is currently on metformin, glipizide, enalapril and amlodipine. She complains of a 6-week history of swelling affecting both her legs, which is causing her significant discomfort. On examination, you note bilateral pitting oedema up to the mid-shins.

WHAT IS OEDEMA?

Oedema is defined as palpable swelling due to the accumulation of fluid within the interstitial space.[1] Oedema may be generalised (affecting multiple body parts or areas) or localised (affecting one particular body part or area). Box 1 shows the causes of oedema. In standing and mobile adults, the most common cause of localised oedema is dependent oedema.

Box 1.

Causes of oedema.

Generalised
• Anaphylaxis	• Medication
• Chronic liver disease/cirrhosis	–Dihydropyridine calcium channel blockers (e.g., amlodipine, nifedipine, felodipine)
• Chronic kidney disease/nephrotic syndrome	– Steroids
• Heart failure	– Oestrogens and progestins
• Protein-losing enteropathy	– NSAIDs
• Hypothyroidism	–Vasodilators: hydralazine, minoxidil, diazoxide
• Pregnancy	– Thiazolidinediones
	–Traditional medications (may contain steroids)
Localised
• Infection	• Venous insufficiency
• Inflammation (gout/pseudo-gout)	• Lymphoedema
• Deep vein thrombosis	• Dependent oedema

NSAIDs: nonsteroidal anti-inflammatory drugs

HOW RELEVANT IS THIS TO MY PRACTICE?

Lower limb oedema is a common presentation encountered by general practitioners (GPs), especially those who attend to older adults with chronic diseases. It should be evaluated thoroughly because lower limb oedema may be the first sign of an underlying systemic illness. Early recognition and prompt referral to a specialist, if necessary, allows for appropriate treatment to be initiated quickly, thereby reducing morbidity and mortality.

WHAT CAN I DO IN MY PRACTICE?

When evaluating an individual with lower limb oedema, the initial step should be to determine if the patient can be evaluated safely in the outpatient setting or if the patient requires urgent referral to the hospital. A patient who is haemodynamically unstable or visibly tachypnoeic should be referred to the emergency department as soon as possible.

If the patient is clinically stable, the GP may proceed to conduct a targeted history and physical examination. The first and most useful step is to determine if the oedema is unilateral or bilateral. This dichotomy quickly narrows down the differentials, allowing the GP to focus on evaluating the relevant causes. As a general rule of thumb, unilateral oedema is associated with localised pathology such as infection or thrombosis. In contrast, bilateral oedema is typically associated with systemic pathology such as organ failure.

APPROACH TO BILATERAL LOWER LIMB OEDEMA

This article focuses on bilateral lower limb oedema. Figure 1 shows a suggested approach to bilateral lower limb oedema.

Figure 1.

Diagnostic algorithm for bilateral lower limb oedema.

History and examination

It is important to establish the onset, duration and progression of the patient’s lower limb swelling. Most patients usually report a gradual onset (weeks to months) of leg swelling that becomes characteristically worse after long periods of standing. Patients with atypical presentation may have a less common cause of bilateral lower limb oedema. For example, if a patient reports leg swelling of a more rapid onset (less than 72 h), there should be a higher suspicion of infection or bilateral deep vein thrombosis. Leg swelling that does not worsen with prolonged standing may point towards myxoedema, as seen in hypothyroidism.

It is important to establish the onset and timing of the lower limb swelling in relation to the initiation of a new medication, as many medications are known to cause lower limb swelling. The swelling seen in medication-induced oedema occurs gradually, with effects usually occurring weeks to months after initiation.[2] Calcium channel blockers (CCBs) are a common culprit, causing lower limb oedema in about 10% of patients.[2] The oedema associated with CCB use is dose dependent and occurs more frequently with dihydropyridine CCBs (e.g. amlodipine, nifidipine, felodipine) than with the non-dihydropyridine CCBs (e.g. diltiazem, verapamil).[2]

Once the nature of the patient’s lower limb swelling is established, the GP should assess the patient for features suggestive of an underlying systemic disorder. Bilateral lower limb oedema is commonly the result of cardiac, renal, hepatic or thyroid dysfunction, and so it is important for GPs to assess for symptoms and signs associated with these diseases [Table 1].

Table 1.

High-yield symptoms and signs.

Disorder	Symptom/sign
Heart failure[3,4]	Orthopnoea or paroxysmal nocturnal
	dyspnoea
	Shortness of breath on exertion
	Reduced effort tolerance
	Third heart sound
Chronic liver disease[5]	Ascites
	Scleral icterus
	Spider naevi
	Palmar erythema
	Paucity of axillary hair
	Testicular atrophy
	Distended umbilical veins
Hypothyroidism[6,7]	Constipation
	Cold intolerance
	Bradycardia
	Delayed deep tendon reflexes
Chronic kidney disease	No sign or symptom that is particularly
	sensitive —diagnosis more reliant on laboratory investigations

The GP should make special effort to palpate for inguinal lymphadenopathy and to examine the patient’s abdomen for any masses. Such masses may cause lower limb swelling through compression of the veins and/or lymphatics draining the affected limbs.

If a patient does not have any symptoms or signs suggestive of an underlying systemic disorder and is not taking a medication known to cause swelling, the bilateral lower limb oedema is most likely due to a localised pathology, such as chronic venous insufficiency or lymphoedema. These entities can be distinguished on physical examination. The first differentiating factor is that the oedema in chronic venous insufficiency is pitting, i.e. the application of firm pressure to the oedematous area results in the formation of an indentation. In contrast, the oedema seen in lymphoedema is usually nonpitting. The second distinguishing factor is the nature of the skin changes observed in both conditions. Patients with chronic venous insufficiency have characteristic changes such as gaiter region hyperpigmentation, stasis eczema, varicose veins, telangiectasias (spider veins) and venous ulcers. These skin changes are absent in patients with lymphoedema, whose skin may take on a cobblestoned, verrucous appearance over time and has a thickened or doughy texture on palpation.

Initial investigations

Before ordering any investigation, one should review the patient’s National Electronic Health Record (NEHR) to check for any abnormal test results that might explain the patient’s oedema. Relevant investigations to look out for include serum creatinine, liver function tests, urine protein/albumin, echocardiograms and venous reflux studies. If there are no recent tests, we recommend ordering limited investigations based on clinical suspicion. Investigations, such as a renal panel, urine dipstick, liver function and thyroid function tests, do not have to be ordered routinely for all patients, but should be considered if a patient has features suggestive of organ dysfunction based on the clinical assessment.

Initial management

The GP may recommend simple lifestyle interventions to alleviate a patient’s lower limb swelling. After sitting or standing for prolonged periods (≥1 h), patients should take a break by elevating the legs, walking briskly or doing calf raises for 10 min. They can also massage the fluid in the swollen limbs upwards in the direction of the heart and elevate their legs with pillows when sleeping.

If drug-induced oedema is suspected, the GP may opt to reduce the dose of the suspected agent or switch to a different drug class. An early review to assess for the resolution of oedema can be arranged subsequently.

If the initial assessment is suggestive of fluid overload from heart failure, kidney dysfunction or liver disease, consider referring the patient for a specialist review. It is also reasonable to start the patient on fluid restriction. Guidelines recommend an initial fluid restriction target of 1.5 L/day.[8] Instructing the patients to limit fluid intake to one standard 1.5 L soft drink bottle per day is a simple and cost-effective solution. Patients should be advised to take into account the fluid in their diet, including soups and desserts. Salt intake should also be moderated. Patients should also monitor and record their weight at home daily.

For patients with venous insufficiency, graded compression stockings are the mainstay of treatment. When prescribing for patients with varicosities and oedema, a tension of 20–30 mmHg is recommended.[9] Medical-grade stockings are available for purchase at many retail pharmacies. Good skin care is also essential in preventing complications such as venous stasis eczema and ulcers. Care must be taken when bathing because soaps and rough-textured towels can irritate skin. Patients should be advised to use a mild, fragrance-free soap substitute, such as an emulsifying ointment or an aqueous cream, as normal soap tends to dry the skin excessively. After bathing, patients should pat the skin dry gently with a soft, clean towel and apply an emollient onto the damp skin within 2 min to lock in the moisture. Emollient should be reapplied as often as needed to keep the skin hydrated. Those with more severe symptoms and complications, such as venous ulcers, should be referred to a vascular surgeon.[9]

If the lower limb swelling is causing significant discomfort and/or affecting the patient’s daily activities, the GP can also consider initiating a loop diuretic such as frusemide. The recommended initial dose of peroral frusemide is 20 mg once daily.[8] It should be noted that furosemide is a potent diuretic that can lead to significant electrolyte depletion, water depletion and pre-renal acute kidney injury. As such, electrolyte levels (in particular, sodium and potassium) and renal function should be monitored closely after the initiation of frusemide. There are no guidelines on the precise timing and frequency, but most GPs would consider doing these tests within 1–2 weeks of initiation. Patients should also be advised to monitor for symptoms suggestive of overdiuresis, such as excessive thirst, worsening lethargy or confusion.

WHEN SHOULD I REFER TO A SPECIALIST?

Specialist referral should be considered when there is suspected organ failure, disease complications requiring advanced intervention or if the underlying cause of the oedema remains uncertain. Referral to a specialist is indicated in the following cases: suspected heart failure; chronic kidney disease (stage 3 onwards); liver cirrhosis; chronic venous insufficiency with severe symptoms and/or complications (e.g. ulcers); recurrent fluid overload; and uncertain aetiology.

If the patient is clinically unstable (i.e. tachypnoeic, hypoxic, hypotensive or having altered mental status), he/she should be referred to the emergency department immediately. If the patient is clinically stable, he/she should be seen by a specialist early, preferably within 2–4 weeks.

TAKE HOME MESSAGES

1. Lower limb swelling is commonly encountered in primary care. Although there are multiple possible causes, a targeted approach grounded in a good history and physical examination is usually sufficient to reach a diagnosis.

2. The first step is to determine if the oedema is unilateral (associated with localised pathology) or bilateral (associated with systemic pathology).

3. Bilateral lower limb oedema is commonly the result of systemic dysfunction (cardiac, renal, hepatic or thyroid). GPs can assess for these disorders by identifying high-yield symptoms and signs.

4. A thorough review of a patient’s NEHR should be done to obtain information on the patient’s past medical history and identify potential culprit medications.

5. Investigations should be ordered in a targeted manner, based on one’s clinical suspicion.

6. Initial management options include lower limb elevation and fluid restriction (1.5 L/day).

7. If the swelling causes significant discomfort and/or affects daily activities, consider initiating a loop diuretic, followed by a check on the patient’s electrolytes and renal function within 1–2 weeks.

8. Specialist referral should be considered when there is organ failure, disease complications requiring advanced intervention or if the underlying cause of the oedema remains uncertain.

Closing Vignette.

You elicit from the history that in addition to bilateral leg swelling, Mrs Tan has been experiencing orthopnoea and shortness of breath on exertion. Although she has been taking amlodipine, which was initiated more than 10 years ago without any recent changes in dose, she had never experienced any leg swelling before this episode. You suspect a diagnosis of congestive cardiac failure and refer Mrs Tan to a cardiologist. Further evaluation reveals that Mrs Tan has ischaemic cardiomyopathy, with a left ventricular ejection fraction of 35% and double-vessel disease noted on coronary angiography. She is initiated on guideline-directed medical therapy and undergoes percutaneous coronary intervention. Her leg swelling subsequently resolves.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

SMC CATEGORY 3B CME PROGRAMME

Online Quiz: https://www.sma.org.sg/cme-programme

Deadline for submission: 6 pm, 09 August 2023

Question		True	False
1.	Oedema is defined as palpable swelling due to the accumulation of fluid within the intravascular space.
2.	In standing and mobile adults, the most common cause of localised oedema is dependent oedema.
3.	Drugs that can cause oedema include steroids, oestrogens and nonsteroidal anti-inflammatory drugs.
4.	All patients with lower limb oedema can be evaluated safely in the outpatient setting.
5.	Patients who are haemodynamically unstable or visibly tachypnoeic should be referred to the emergency department as soon as possible.
6.	The swelling seen in medication-induced oedema occurs gradually, with effects usually occurring weeks to months after initiation.
7.	The oedema associated with calcium channel blockers (CCBs) occurs more frequently with non-dihydropyridine CCBs than with dihydropyridine CCBs.
8.	The skin in patients with chronic venous insufficiency may take on a cobblestoned, verrucous appearance over time.
9.	A common cause of bilateral lower limb oedema is hyperthyroidism.
10.	If a patient reports leg swelling of more rapid onset (over hours to days), there is a low suspicion of bilateral deep vein thrombosis.
11.	The presence of orthopnoea and shortness of breath on exertion increases the likelihood that lower limb oedema is due to heart failure.
12.	The presence of palmar erythema and spider naevi decreases the likelihood that lower limb oedema is due to chronic liver disease.
13.	Intra-abdominal masses can cause lower limb swelling through the compression of veins and/or lymphatics.
14.	In most cases, the oedema seen in lymphoedema is pitting, while the oedema seen in chronic venous insufficiency is nonpitting.
15.	A renal function test, thyroid function test and urine dipstick should be routinely ordered for all patients with bilateral lower limb oedema.
16.	The recommended initial target for fluid restriction is 1.5 L/day for a patient with fluid overload.
17.	When initiating frusemide, an initial dose of 40 mg twice daily is recommended.
18.	After starting a patient on frusemide, general practitioners (GPs) should consider monitoring the patient’s renal function and electrolyte levels within 1–2 weeks.
19.	For patients with venous insufficiency, good skin care is not essential in preventing complications such as venous stasis eczema and ulcers.
20.	GPs should refer all patients with bilateral lower limb oedema to a specialist.